Safety and Immunogenicity Study of BCG, H4:IC31, and H56:IC31 Revaccination in Healthy Adolescents

• Sponsor: Aeras (Other)
• Overall Status: Completed
• CT.gov ID: NCT02378207
• Collaborator: HIV Vaccine Trials Network (Other), Sanofi Pasteur, a Sanofi Company (Industry), Statens Serum Institut (Other)
• Enrollment: 84
• Location: 1
• Arms: 4
• Duration (Months): 19.3
• Patients Per Site Per Month: 4.3

Study Details

Study Description

Brief Summary

The aims of the phase 1b trial described here are to facilitate identification of assays and immune responses that could then be evaluated as correlates of risk and correlates of protection in efficacy studies and ultimately to provide leads for biomarkers of protection against tuberculosis. This study will complement one ongoing study (NCT02075203) evaluating the prevention of M. Tuberculosis infection using H4:IC31 (also known as AERAS-404).

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis	Biological: H4:IC31; Biological: H56:IC31; Biological: BCG; Biological: Control Sodium Chloride 0.9%	Phase 1

Detailed Description

This study proposes to further evaluate the safety and immunogenicity of H4:IC31, H56:IC31, and BCG revaccination. The study will be conducted in previously BCG vaccinated healthy adolescents, and will entail a thorough immunogenicity evaluation of these regimens incorporating unbiased systems vaccinology approaches and novel assessments of baseline and elicited responses that may impact vaccine responses. A major goal for this study is to generate immunological data on a wide range of immune responses using a variety of approaches including validated assessments, unbiased strategies, and novel exploratory assays to increase the likelihood of detecting responses correlating with risk or protection in the prevention of infection study. Investigators contributing to the proposed study have participated in a correlates analysis for an HIV vaccine exhibiting modest efficacy in which 2 correlates of risk were identified.

An additional aim of this study is to explore factors affecting vaccine induced responses that may also impact efficacy. For example, it is hypothesized that exposure to environmental mycobacteria may alter protection provided by BCG vaccination. Reagents for evaluating levels of exposure to environmental mycobacteria are in development as part of a concurrent collaborative study. An exploratory objective for this trial is to apply these reagents to examine whether such exposures influence immune responses elicited by the study vaccine and regimens.

Study Design

• Study Type: Interventional
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Randomized, Placebo-controlled, Partially Blinded Phase 1b Clinical Trial to Evaluate the Safety and Immunogenicity of BCG Revaccination, H4:IC31, and H56:IC31 in Healthy, HIV-1-Uninfected Adolescent Participants
• Study Start Date: May 1, 2015
• Actual Primary Completion Date: Oct 31, 2016
• Actual Study Completion Date: Dec 9, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 H4:IC31 15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.	Biological: H4:IC31; H4 contains Mtb antigens Ag85B and TB10.4
Experimental: Group 2 H56:IC31 5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.	Biological: H56:IC31; H56 contains Mtb antigens ESAT-6, and Rv2660c
Active Comparator: Group 3 BCG (2-8 x 105 CFU) Administered IM as 0.1 mL in either deltoid muscle at Day 0.	Biological: BCG
Placebo Comparator: Group 4 Control Sodium Chloride 0.9% Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.	Biological: Control Sodium Chloride 0.9%

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events [Up to 8 months]

   The number of solicited and unsolicited adverse events (AEs), including serious adverse events (SAEs), recorded post-vaccination for all participants.

2. Percentage of Participants With Response Rates to TB Antigens as Compared to Baseline [Days 70 and 168]

   Flow cytometry was used to examine TB Mb-specific CD4+ and CD8+ T-cell responses using the ICS assay. The antigens used to stimulate cells in this assay included peptide pools for the vaccine-matched proteins (Ag85B, ESAT-6, Rv2660c, and TB 10.4) as well as complex TB antigens (TB whole cell lysate [TB WCL], and BCG Pasteur strain.

Secondary Outcome Measures

1. Evaluate Humoral Responses Elicited by the Different Vaccine Regimens. [Up to day 168.]

   Vaccine-specific binding antibodies elicited by the vaccine regimens as determined by multiplex antibody assay and/or enzyme-linked immunosorbent assay (ELISA).

2. * Evaluate Immune Response From Vaccine Regimens by Measuring Early (Innate) Vaccine-induced Peripheral Blood Transcription Profiles; Determine Which Responses Are Associated With Antigen-specific Adaptive Responses * Evaluate Adaptive Immune Response. [Up to day 168]

   Changes in gene expression measured in longitudinally-collected blood samples relative to samples collected at baseline. The transcriptional profiles will be correlated with antigen-specific adaptive responses measured in Primary objective 2. Transcriptional analysis of antigen-stimulated peripheral blood mononuclear cells (PBMC) at 2 weeks post vaccination will be performed..

3. Evaluate Changes in Innate Cells in Response to the Vaccine Regimens [Up to day 168]

   Blood concentrations of innate immune cell populations including lymphocyte populations, dendritic cells, monocytes, and granulocytes before and after vaccination

4. Measure Non-classical Major Histocompatibility Complex (MHC)-Restricted T-cell Vaccine-induced Responses, Such as to Mycobacterial Lipids (CD1-restricted) and Metabolites (MR1-restricted). [Up to day 168]

   Frequency of CD4+, CD8+, and CD4/CD8 double-negative T-cell responses restricted by CD1 (recognizing specific Mtb lipids) before and after BCG revaccination in Group 3 participants. Frequency of mucosal-associated invariant T-cells (MAIT) restricted by MR1 (recognizing vitamin B metabolites) before and after BCG revaccination in Group 3 participants

5. Evaluate QFT-GIT and ESAT-6 Free IGRA Discordance and Conversion/Reversion Rate During the Course of the Trial. [Up to day 168]

   Magnitude and positivity of interferon (IFN)-γ release using QFT-GIT ELISA in QFT-GIT tests. Magnitude and positivity of IFN-γ release using QFT-GIT ELISA in ESAT-6 free IGRAs.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Age of 12 to ≤ 17 years at enrollment

2. Minimum weight ≥ 40 kg

3. Previous BCG vaccination at least 5 years ago documented by scarification or medical card

4. No evidence of active TB disease, as determined by history, physical examination and, if deemed appropriate, sputum investigation and / or chest x-ray.

5. Negative QFT-GIT test at screening, using the manufacturer's recommended threshold of 0.35 IU/mL

6. Assessed by the clinic staff as being at low risk for HIV infection

7. Hemoglobin ≥ 11.7 g/dL for females, ≥ 12.5 g/dL for males

8. Negative HIV-1 and -2 blood test

9. Agree to consistently use effective contraception for sexual activity that could lead to pregnancy from at least 20 days prior to enrollment through the last required protocol clinic visit.

(additional minor criteria not added due to space constraints)

Exclusion Criteria:

1. Blood products received within 120 days before first vaccination

2. Investigational research agents received within 182 days before first vaccination

3. Intent to participate in another study of an investigational research agent during the planned duration of the HVTN 602 / AERAS A-042 study

4. Pregnant or breastfeeding

5. History of alcohol or drug abuse

6. A significant contact with active TB disease: for example, shared residency with an individual receiving anti-TB treatment, or with an individual known to have incompletely treated culture or smear positive TB

7. TB prophylaxis within 90 days prior to enrollment

8. History of treatment for active TB disease or latent Mtb infection

9. Positive and indeterminate QFT-GIT result

10. Received a tuberculin skin test (TST) within 90 days prior to enrollment

11. Vaccines and other Injections

12. Immunosuppressive medications received within 168 days before first vaccination.

13. Serious adverse reactions to vaccines including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain.

14. Immunoglobulin received within 60 days before first vaccination

15. Autoimmune disease Not excluded: mild, well-controlled psoriasis

16. Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. Including but not limited to: Diabetes mellitus type 1 or type 2, Thyroidectomy, or Thyroid disease, Asthma, Asplenia, Bleeding disorders, malignancy, Seizure disorder, and Angioedema

(additional minor criteria not added due to space constraints)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Desmond Tutu HIV Foundation	Cape Town		South Africa

Sponsors and Collaborators

• Aeras
• HIV Vaccine Trials Network
• Sanofi Pasteur, a Sanofi Company
• Statens Serum Institut

Investigators

• Study Chair: Linda-Gail Bekker, MD, Desmond Tutu HIV Centre
• Study Chair: Jim Kublin, MD, HVTN Core, FHCRC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Aeras
• ClinicalTrials.gov Identifier: NCT02378207
• Other Study ID Numbers: HVTN 602 / AERAS A-042
• First Posted: Mar 4, 2015
• Last Update Posted: Nov 18, 2019
• Last Verified: Jan 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Tuberculosis

Study Results

Participant Flow

Arm/Group Title	Group 1 H4:IC31	Group 2 H56:IC31	Group 3 BCG (2-8 x 105 CFU)	Group 4 Control Sodium Chloride 0.9%
Arm/Group Description	15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.	5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.	Administered ID as 0.1 mL in either deltoid muscle at Day 0.	Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.
Period Title: Overall Study
STARTED	24	24	24	12
COMPLETED	24	21	22	11
NOT COMPLETED	0	3	2	1

Baseline Characteristics

Arm/Group Title	Group 1 H4:IC31	Group 2 H56:IC31	Group 3 BCG (2-8 x 105 CFU)	Group 4 Control Sodium Chloride 0.9%	Total
Arm/Group Description	15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56. n=24	5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56. n=24	Administered ID as 0.1 mL in either deltoid muscle at Day 0. n=24	Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56. n=24	Total of all reporting groups
Overall Participants	24	24	24	12	84
Age (Count of Participants)
<=18 years	24 100%	24 100%	24 100%	12 100%	84 100%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.8 (1.42)	13.7 (1.46)	14.5 (1.47)	13.2 (1.11)	13.9 (1.45)
Sex: Female, Male (Count of Participants)
Female	15 62.5%	13 54.2%	11 45.8%	6 50%	45 53.6%
Male	9 37.5%	11 45.8%	13 54.2%	6 50%	39 46.4%
Region of Enrollment (participants) [Number]
South Africa	24 100%	24 100%	24 100%	12 100%	84 100%
Participants: QuantiFERON-TB Gold In-Tube (QFT-GIT)-negative, HIV-negative, and BCG vaccinated (Count of Participants)
Count of Participants [Participants]	24 100%	24 100%	24 100%	12 100%	84 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events
Description	The number of solicited and unsolicited adverse events (AEs), including serious adverse events (SAEs), recorded post-vaccination for all participants.
Time Frame	Up to 8 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1 H4:IC31	Group 2 H56:IC31	Group 3 BCG (2-8 x 105 CFU)	Group 4 Control Sodium Chloride 0.9%
Arm/Group Description	15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.	5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.	Administered ID as 0.1 mL in either deltoid muscle at Day 0.	Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.
Measure Participants	24	24	24	12
Number [participants]	22 91.7%	20 83.3%	24 100%	10 83.3%

2. Primary Outcome

Title	Percentage of Participants With Response Rates to TB Antigens as Compared to Baseline
Description	Flow cytometry was used to examine TB Mb-specific CD4+ and CD8+ T-cell responses using the ICS assay. The antigens used to stimulate cells in this assay included peptide pools for the vaccine-matched proteins (Ag85B, ESAT-6, Rv2660c, and TB 10.4) as well as complex TB antigens (TB whole cell lysate [TB WCL], and BCG Pasteur strain.
Time Frame	Days 70 and 168

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1 H4:IC31	Group 2 H56:IC31	Group 3 BCG (2-8 x 105 CFU)	Group 4 Control Sodium Chloride 0.9%
Arm/Group Description	15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.	5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.	Administered ID as 0.1 mL in either deltoid muscle at Day 0.	Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.
Measure Participants	24	24	24	12
Response rates to Ag85B on Day 70	40.0 166.7%	45.0 187.5%	0.0 0%	0.0 0%
Response rates to TB10.4 on Day 70	21.1 87.9%	5.6 23.3%	5.9 24.6%	0.0 0%
Response rates to Ag85B on Day 168	21.7 90.4%	9.5 39.6%	4.3 17.9%	0.0 0%
Response rate to TB10.4 on Day 168	8.7 36.3%	0.0 0%	0.0 0%	0.0 0%

3. Secondary Outcome

Title	Evaluate Humoral Responses Elicited by the Different Vaccine Regimens.
Description	Vaccine-specific binding antibodies elicited by the vaccine regimens as determined by multiplex antibody assay and/or enzyme-linked immunosorbent assay (ELISA).
Time Frame	Up to day 168.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	* Evaluate Immune Response From Vaccine Regimens by Measuring Early (Innate) Vaccine-induced Peripheral Blood Transcription Profiles; Determine Which Responses Are Associated With Antigen-specific Adaptive Responses * Evaluate Adaptive Immune Response.
Description	Changes in gene expression measured in longitudinally-collected blood samples relative to samples collected at baseline. The transcriptional profiles will be correlated with antigen-specific adaptive responses measured in Primary objective 2. Transcriptional analysis of antigen-stimulated peripheral blood mononuclear cells (PBMC) at 2 weeks post vaccination will be performed..
Time Frame	Up to day 168

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Evaluate Changes in Innate Cells in Response to the Vaccine Regimens
Description	Blood concentrations of innate immune cell populations including lymphocyte populations, dendritic cells, monocytes, and granulocytes before and after vaccination
Time Frame	Up to day 168

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Measure Non-classical Major Histocompatibility Complex (MHC)-Restricted T-cell Vaccine-induced Responses, Such as to Mycobacterial Lipids (CD1-restricted) and Metabolites (MR1-restricted).
Description	Frequency of CD4+, CD8+, and CD4/CD8 double-negative T-cell responses restricted by CD1 (recognizing specific Mtb lipids) before and after BCG revaccination in Group 3 participants. Frequency of mucosal-associated invariant T-cells (MAIT) restricted by MR1 (recognizing vitamin B metabolites) before and after BCG revaccination in Group 3 participants
Time Frame	Up to day 168

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Evaluate QFT-GIT and ESAT-6 Free IGRA Discordance and Conversion/Reversion Rate During the Course of the Trial.
Description	Magnitude and positivity of interferon (IFN)-γ release using QFT-GIT ELISA in QFT-GIT tests. Magnitude and positivity of IFN-γ release using QFT-GIT ELISA in ESAT-6 free IGRAs.
Time Frame	Up to day 168

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	AEs: 7 days post each vaccination Unsolicited AEs: 28 days post each vaccination Solicited injection-site reaction AEs: BCG group - 84 days post each vaccination; H4:IC31/placebo - 28 days post each vaccination; H56:IC31/placebo - 28 days post each vaccination SAEs, AEs of special interest, SUSARs: through day 224
Arm/Group Title	Group 1 H4:IC31		Group 2 H56:IC31		Group 3 BCG (2-8 x 105 CFU)		Group 4 Control Sodium Chloride 0.9%
Arm/Group Description	15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56. H4:IC31		5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56. H56:IC31		Administered ID as 0.1 mL in either deltoid muscle at Day 0. BCG		Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56. Control Sodium Chloride 0.9%
All Cause Mortality
	Group 1 H4:IC31		Group 2 H56:IC31		Group 3 BCG (2-8 x 105 CFU)		Group 4 Control Sodium Chloride 0.9%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)		0/24 (0%)		0/12 (0%)
Serious Adverse Events
	Group 1 H4:IC31		Group 2 H56:IC31		Group 3 BCG (2-8 x 105 CFU)		Group 4 Control Sodium Chloride 0.9%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		1/24 (4.2%)		1/24 (4.2%)		0/12 (0%)
Infections and infestations
Impetigo	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0
Injury, poisoning and procedural complications
Road traffic accident	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Investigations
Cardiac murmur functional	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0
Other (Not Including Serious) Adverse Events
	Group 1 H4:IC31		Group 2 H56:IC31		Group 3 BCG (2-8 x 105 CFU)		Group 4 Control Sodium Chloride 0.9%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/24 (91.7%)		20/24 (83.3%)		24/24 (100%)		10/12 (83.3%)
Cardiac disorders
Palpitations	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1
Tachycardia	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	2/12 (16.7%)	4
Gastrointestinal disorders
Abdominal pain	0/24 (0%)	0	0/24 (0%)	0	2/24 (8.3%)	2	0/12 (0%)	0
Aphthous stomatitis	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0
Diarrhoea	1/24 (4.2%)	1	1/24 (4.2%)	3	6/24 (25%)	6	2/12 (16.7%)	2
Nausea	3/24 (12.5%)	3	5/24 (20.8%)	7	3/24 (12.5%)	3	1/12 (8.3%)	1
Vomiting	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
General disorders
Chills	5/24 (20.8%)	7	6/24 (25%)	7	2/24 (8.3%)	3	2/12 (16.7%)	3
Fatigue	6/24 (25%)	10	7/24 (29.2%)	12	8/24 (33.3%)	9	1/12 (8.3%)	1
Feeling cold	1/24 (4.2%)	1	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Implant site swelling	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0
Injection site erythema	2/24 (8.3%)	3	4/24 (16.7%)	6	0/24 (0%)	0	0/12 (0%)	0
Injection site pain	14/24 (58.3%)	16	13/24 (54.2%)	21	0/24 (0%)	0	3/12 (25%)	6
Injection site pruritus	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1
Injection site swelling	3/24 (12.5%)	4	4/24 (16.7%)	4	0/24 (0%)	0	0/12 (0%)	0
Pyrexia	2/24 (8.3%)	2	2/24 (8.3%)	2	0/24 (0%)	0	1/12 (8.3%)	1
Vaccination site discolouration	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Vaccination site erythema	0/24 (0%)	0	0/24 (0%)	0	8/24 (33.3%)	8	0/12 (0%)	0
Vaccination site exfoliation	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Vaccination site induration	0/24 (0%)	0	0/24 (0%)	0	10/24 (41.7%)	10	0/12 (0%)	0
Vaccination site pain	0/24 (0%)	0	0/24 (0%)	0	14/24 (58.3%)	18	0/12 (0%)	0
Vaccination site pruritus	0/24 (0%)	0	0/24 (0%)	0	2/24 (8.3%)	2	0/12 (0%)	0
Vaccination site rash	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Vaccination site scab	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Vaccination site scar	0/24 (0%)	0	0/24 (0%)	0	3/24 (12.5%)	3	0/12 (0%)	0
Vaccination site swelling	0/24 (0%)	0	0/24 (0%)	0	13/24 (54.2%)	13	0/12 (0%)	0
Vaccination site ulcer	0/24 (0%)	0	0/24 (0%)	0	7/24 (29.2%)	7	0/12 (0%)	0
Infections and infestations
Cellulitis	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0
Folliculitis	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1
Gastroenteritis viral	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Influenza	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Lower respiratory tract infection	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0
Pharyngitis	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0
Rhinitis	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Trichomoniasis	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0
Upper respiratory tract infection	1/24 (4.2%)	1	2/24 (8.3%)	2	0/24 (0%)	0	0/12 (0%)	0
Vaccination site abscess	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Viral upper respiratory tract infection	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1
Injury, poisoning and procedural complications
Contusion	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0
Investigations
Blood pressure diastolic increased	5/24 (20.8%)	7	2/24 (8.3%)	5	4/24 (16.7%)	4	1/12 (8.3%)	1
Blood pressure systolic increased	4/24 (16.7%)	4	5/24 (20.8%)	7	4/24 (16.7%)	4	2/12 (16.7%)	2
Neutrophil count decreased	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1
Protein urine	5/24 (20.8%)	6	1/24 (4.2%)	1	2/24 (8.3%)	2	2/12 (16.7%)	2
White blood cell count increased	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0	2/12 (16.7%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	1/24 (4.2%)	1	3/24 (12.5%)	5	3/24 (12.5%)	4	1/12 (8.3%)	2
Myalgia	2/24 (8.3%)	2	5/24 (20.8%)	6	4/24 (16.7%)	4	1/12 (8.3%)	1
Nervous system disorders
Dizziness	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0
Headache	7/24 (29.2%)	9	6/24 (25%)	8	8/24 (33.3%)	8	2/12 (16.7%)	2
Pregnancy, puerperium and perinatal conditions
Haemorrhage in pregnancy	0/24 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/12 (0%)	0
Renal and urinary disorders
Haematuria	2/24 (8.3%)	2	3/24 (12.5%)	3	0/24 (0%)	0	0/12 (0%)	0
Proteinuria	3/24 (12.5%)	3	2/24 (8.3%)	3	1/24 (4.2%)	1	0/12 (0%)	0
Respiratory, thoracic and mediastinal disorders
Nasal congestion	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Skin and subcutaneous tissue disorders
Rash	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0	0/12 (0%)	0
Rash papular	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.